ArticleFrontiers in aging neuroscience2020
Manganese Exposure Aggravates β-Amyloid Pathology by Microglial Activation.
Article in Frontiers in aging neuroscience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Pooled it
- Trace Elements Dyshomeostasis and Toxic Metals Neurotoxicity in Neurodegenerative Diseases.Biological trace element research · 2026Review
- Downregulation of the L-PGDS/15d-PGJ2 Pathway Is Associated with Manganese-Induced Neuroinflammation and Cognitive Impairment Involving C/EBPβ and MMP9.Antioxidants (Basel, Switzerland) · 2026Article
- Associations of blood heavy metals with cognitive function in older US adults: single and mutually adjusted effects.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Observational
- Imbalance of the Arachidonic Acid Metabolism in Neuroinflammation and Cognition Caused by Manganese Exposure: Downregulation of 15d-PGJ2 Levels and Validation of MMP9 as a Target.Environment & health (Washington, D.C.) · 2026Article
- Removal of Toxic Metabolites-Chelation: Manganese Disorders.Journal of inherited metabolic disease · 2025Review
- Impact of Manganese on Neuronal Function: An Exploratory Multi-Omics Study on Ferroalloy Workers in Brescia, Italy.Brain sciences · 2025Article
- CAD (Cath. a-Differentiated) Cells Produce Dopamine along with Dopamine-Synthesizing Enzymes.Neurochemical research · 2025Article
- D-ribose-L-cysteine Attenuates manganese-induced Oxidative Stress, Neuromorphological Deficits, Bax/Bcl-2 Response and TNF-α/ERK Signalling in Rats.Neurochemical research · 2025Article
- The Role of Epigenetics in Manganese Neurotoxicity: An Update with a Focus on Non-Coding RNAs and Histone Modifications.Neurochemical research · 2025Review
- Signal Transduction Associated with Mn-induced Neurological Dysfunction.Biological trace element research · 2024Review
- Consequences of Disturbing Manganese Homeostasis.International journal of molecular sciences · 2023Review
- Associations of ambient manganese exposure with brain gray matter thickness and white matter hyperintensities.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Article
- Manganese Ion-Induced Amyloid Fibrillation Kinetics of Hen Egg White-Lysozyme in Thermal and Acidic Conditions.ACS omega · 2023Article
- Microglial Activation in Metal Neurotoxicity: Impact in Neurodegenerative Diseases.BioMed research international · 2023Review
- Manganese-Induced Toxicity inInternational journal of molecular sciences · 2022Article
- Exposing the role of metals in neurological disorders: a focus on manganese.Trends in molecular medicine · 2022Review
- Endoplasmic reticulum stress and mitochondrial dysfunctions in metal-induced neurological pathology.Journal of neurobiology and physiology · 2022Article
- Cognitive impact of exposure to airborne particles captured by brain imaging.Advances in neurotoxicology · 2022Article
- An Overview of Several Inhibitors for Alzheimer's Disease: Characterization and Failure.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human epidemiological evidence and animal experimental data suggest that chronic manganese (Mn) exposure increases the risk of Alzheimer's disease (AD) and amyloid plaques, a hallmark of AD brain pathology, but the underlying mechanisms were not fully understood. Using the transgenic APP/PS1/Tau triple transgenic AD (3×Tg-AD) mouse model and mouse-derived microglia and neuroblastoma cell lines, we found that chronic 5-month Mn treatment increased beta amyloid peptide (Aβ) expression and Aβ plaques in the cerebral cortex and hippocampus in these 3×Tg-AD mice. Furthermore, we found that the β- and γ-secretase cleavage activities were markedly increased, while α-secretase cleavage activity was reduced in the brain of Mn-treated AD mice; these effects increase Aβ production and thus are amyloidogenic. Equally important, Mn treatment alone did not alter β-secretase 1 (BACE1) gene expression or Aβ production in amyloidogenic mutant amyloid precursor protein (APP) gene hAPPsw-transfected N2a cells (APPsw-N2a), but in APPsw-N2a cells either co-cultured with microglia or cultured with microglia-conditioned media, Mn exposure increased BACE1 expression and amyloidogenesis. We further determined that Mn exposure promoted the activation of microglia both in 3×Tg-AD mouse brains and in cultured microglia cells, and increased the secretion of the inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Taken together, these results suggest that Mn may increase the release of IL-1β and TNF-α from microglia that in turn stimulates the expression of BACE1 gene and protein and consequently Aβ production; this novel molecular mechanism not only advances our understanding about the amyloidogenic effect of chronic Mn exposure reported for special human populations but also indicates Mn dyshomeostasis as a potential contributor to AD pathogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.